Breast cancer accounts for 250,000 new cancer diagnoses annually – making it a significant health burden.  Inherited mutations in Breast Cancer susceptibility (BRCA)-1 or 2 genes significantly increase the likelihood of cancer development.  Upon diagnosis, women with BRCA-1 mutations are more likely to present at a younger age and with a more aggressive phenotype.   Despite advances in screening and treatment, breast cancer incidence and mortality rates have remained constant over the past three decades, underscoring the need for innovative treatment strategies, particularly immunotherapy.  In order for immunotherapy to be effective, one must have a functioning immune system. Preliminary studies indicate a profound reduction in natural killer T (NKT) cells in women with BRCA mutations.  Similarly, in a BRCA-1 mutant mouse model, there is a 70-85% decrease in NKT cells in the periphery and in the thymus.  NKT cells play a critical role in cancer immune surveillance, thus we hypothesize that mutations in BRCA lead to impaired NKT cell development and this loss contributes to cancer development.  NKT cell development diverges from conventional T cells at the double positive stage where they divert into a developmental pathway characterized by four distinct stages.  This study aims to determine at which stage in thymic development NKT cells are lost in BRCA-1 mutant mice, and the mechanism accounting for the paucity of NKT cells in the periphery.  BRCA-1 mutant NKT cells are primarily restrained in stage 2 of development with very few progressing to stage 3.    Importantly, this research identifies a major deficit in host anti-tumor immunity. This work will aid in understanding the mechanisms by which BRCA-1 regulates NKT cell development, and may lead to the development of novel immunotherapeutic strategies.